Diphenamid (CASRN 957-51-7)

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR Diphenamid

File First On-Line 09/30/1987

Category (section)

Status

Last Revised

Oral RfD Assessment (I.A.)

on-line

03/01/1991

Inhalation RfC Assessment (I.B.)

no data

Carcinogenicity Assessment (II.)

no data

_I.
Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A.
Reference Dose for Chronic Oral Exposure (RfD)

The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed
in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Please refer
to the Background Document for an elaboration of these concepts. RfDs
can also be derived for the noncarcinogenic health effects of substances
that are also carcinogens. Therefore, it is essential to refer to other
sources of information concerning the carcinogenicity of this substance.
If the U.S. EPA has evaluated this substance for potential human carcinogenicity,
a summary of that evaluation will be contained in Section II of this file.

__I.A.1.
Oral RfD Summary

Critical Effect

Experimental Doses*

UF

MF

RfD

Liver toxicity

2-Year Dog Feeding
Study

Upjohn Co., 1966a

NOEL: 3 mg/kg/day

LEL: 10 mg/kg/day

100

1

3E-2
mg/kg/day

*Conversion Factors -- none

__I.A.2. Principal and Supporting Studies (Oral RfD)

Groups of purebred beagle dogs, 3 of each sex, were fed 0, 3, 10, or 30
mg/kg/day diphenamid for 2 years. Daily observations were made for the
occurrence of untoward clinical signs, changes in food consumption, behavioral
changes, stool consistency, urinary excretion, and indications of emesis.
Histopathologic observations revealed no distinction between treated and
control dogs, with the exception of an increase in portal macrophages and
fibroblasts in the 10 and 30 mg/kg/day groups. A slight increase in liver
weight occurred in the 10 and 30 mg/kg/day groups. At 30 mg/kg/day these
effects were noted in a greater number of dogs.

__I.A.3.
Uncertainty and Modifying Factors (Oral RfD)

UF — Based on a chronic exposure study, an uncertainty factor of 100 was used
to account for the inter- and intraspecies differences.

__I.A.5.
Confidence in the Oral RfD

Study — Medium
Database — Medium
RfD — Medium

The principal study appears to be of acceptable quality and is given a medium
confidence rating. The database on chronic toxicity is incomplete, and is,
therefore, given a medium confidence. Medium confidence in the RfD follows.

__I.A.6.
EPA Documentation and Review of the Oral RfD

Pesticide Registration Files

Agency Work Group Review — 06/10/1986, 03/18/1987

Verification Date — 03/18/1987

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Diphenamid conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.

__I.A.7.
EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this
assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX)
or hotline.iris@epa.gov (internet address).

Drinking Water Health Advisories,
EPA Regulatory Actions, and Supplementary Data were removed from IRIS
on or before April 1997. IRIS users were directed to the appropriate
EPA Program Offices for this information.